Infrared spectroscopy is the technique of choice for chemical identification of biomolecules through their vibrational fingerprints. However, infrared light interacts poorly with nanometric-size molecules. We exploit the unique electro-optical properties of graphene to demonstrate a high-sensitivity tunable plasmonic biosensor for chemically specific label-free detection of protein monolayers. The plasmon resonance of nanostructured graphene is dynamically tuned to selectively probe the protein at different frequencies and extract its complex refractive index. Additionally, the extreme spatial light confinement in graphene—up to two orders of magnitude higher than in metals—produces an unprecedentedly high overlap with nanometric biomolecules, enabling superior sensitivity in the detection of their refractive index and vibrational fingerprints. The combination of tunable spectral selectivity and enhanced sensitivity of graphene opens exciting prospects for biosensing.

A multitude of biological processes are enabled by complex interactions between lipid membranes and proteins. To understand such dynamic processes, it is crucial to differentiate the constituent biomolecular species and track their individual time evolution without invasive labels. Here, we present a label-free mid-infrared biosensor capable of distinguishing multiple analytes in heterogeneous biological samples with high sensitivity. Our technology leverages a multi-resonant metasurface to simultaneously enhance the different vibrational fingerprints of multiple biomolecules. By providing up to 1000-fold near-field intensity enhancement over both amide and methylene bands, our sensor resolves the interactions of lipid membranes with different polypeptides in real time. Significantly, we demonstrate that our label-free chemically specific sensor can analyze peptide-induced neurotransmitter cargo release from synaptic vesicle mimics. Our sensor opens up exciting possibilities for gaining new insights into biological processes such as signaling or transport in basic research as well as provides a valuable toolkit for bioanalytical and pharmaceutical applications.

The physics of electrons, photons, and their plasmonic interactions changes greatly when one or more dimensions are reduced down to the nanometer scale 1 . For example, graphene shows unique electrical, optical, and plasmonic properties, which are tunable through gating or chemical doping 2-5 . Similarly, ultrathin metal films (UTMFs) down to atomic thickness can possess new quantum optical effects 6,7 , peculiar dielectric properties 8 , and predicted strong plasmons 9,10 . However, truly two-dimensional plasmonics in metals has so far elusive because of the difficulty in producing large areas of sufficiently thin continuous films. Thanks to a deposition technique that allows percolation even at 1 nm thickness, we demonstrate plasmons in few-nanometer gold UTMFs, with clear evidence of new dispersion regimes and large electrical tunability. Resonance peaks at 1.5-5 m wavelengths are shifted by hundreds of nanometers and amplitude-modulated by tens of per cent through gating using relatively low voltages. The results suggest ways to use metals in plasmonic applications, such as electrooptic modulation, bio-sensing, and smart windows. Main text:Since ancient times, plasmons in nanoparticles of noble metals such as silver and gold have been used to color glass, culminating during the last two decades with a remarkable broadening of the use of plasmon excitations triggered by an improved understanding of their origin and behaviour, as well as by the availability of more sophisticated means to synthesize and pattern the metals [11][12][13] . New applications promise to have an impact on the optical industry: for example, super lenses allowing unprecedented sub-diffraction-limited optical imaging 14 , metasurfaces providing on-chip functionality in ultrathin form factor 15 , light modulation 16 , compact biosensors 17 and electrochemical effects that can be used in smart windows 18 . All